Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome

Abstract:

Human parvovirus B19 infection has been associated with various clinical manifestations of a rheumatic nature such as arthritis, fatigue, and chronic fatigue syndrome (CFS), which can persist for years after the acute phase.

The authors have demonstrated recently that acute B19 infection is accompanied by raised circulating levels of IL-1b, IL-6, TNF-a, and IFN-g and that raised circulating levels of TNF-a and IFN-g persist and are accompanied by MCP-1 in those patients who develop CFS.

A resolution of clinical symptoms and cytokine dysregulation after intravenous immunoglobulin (IVIG) therapy, which is the only specific treatment for parvovirus B19 infection, also has been reported. Although CFS may be caused by various microbial and other triggers, that triggered by B19 virus is clinically indistinguishable from idiopathic CFS and exhibits similar cytokine abnormalities and may represent an accessible model for the study of CFS.

 

Source: Kerr JR, Tyrrell DA. Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr Pain Headache Rep. 2003 Oct;7(5):333-41. http://www.ncbi.nlm.nih.gov/pubmed/12946285

 

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome

Abstract:

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

 

Source: Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN.  Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis. 2003 May 1;36(9):e100-6. Epub 2003 Apr 22. http://cid.oxfordjournals.org/content/36/9/e100.long (Full article)

 

Chronic fatigue syndrome and arthralgia following parvovirus B19 infection

Abstract:

OBJECTIVE: To determine the incidence of arthralgia and fatigue complicating B19 infection, along with associated B19 markers and autoantibodies.

METHODS: We studied patients with acute B19 infection (n = 51), patients followed from the time of acute B19 infection (mean 22.5 mo) (n = 39), and healthy controls (n = 50). Clinical details were collected using a questionnaire and blood was tested for B19 markers and autoantibodies.

RESULTS: Acute B19 arthralgia occurred in 31 patients and was associated with female sex (p = 0.007) and age > 20 years (p = 0.02). Acute B19 fatigue occurred in 8 patients and was not significantly associated with any marker. At followup, symptoms consisted of arthralgia (n = 5), arthralgia and fatigue (n = 6), fatigue (n = 7), lymphadenopathy (n = 1), and purpura due to thrombocytopenia (n = 2). Chronic B19 arthralgia was associated with persistent B19 viremia (p = 0.029). Comparison of the B19 followup group with the controls revealed a significantly increased prevalence of arthralgia (p = 0.0002), fatigue (p < 0.0001), and all other markers. Chronic B19 arthralgia was associated with both acute B19 arthralgia (p = 0.0168) and positive ANA at acute infection (p = 0.0043). Chronic B19 fatigue was associated with acute B19 fatigue (p = 0.011). Five patients fulfilled the Centers for Disease Control criteria for a diagnosis of chronic fatigue syndrome (CFS) and one of these was negative for serum anti-B19 IgG at followup by both Western blot and immunofluorescence. However, there was no characteristic pattern of B19 markers/autoantibodies in patients with B19 associated chronic fatigue.

CONCLUSION: CFS may follow acute parvovirus B19 infection; however, attribution of a case of CFS to B19 infection may be extremely difficult in the absence of serological confirmation of acute infection at fatigue onset.

 

Source: Kerr JR, Bracewell J, Laing I, Mattey DL, Bernstein RM, Bruce IN, Tyrrell DA. Chronic fatigue syndrome and arthralgia following parvovirus B19 infection. J Rheumatol. 2002 Mar;29(3):595-602. http://www.ncbi.nlm.nih.gov/pubmed/11911112

 

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

Abstract:

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50).

At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months).

In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275).

Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.

 

Source: Kerr JR, Barah F, Mattey DL, Laing I, Hopkins SJ, Hutchinson IV, Tyrrell DA. Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol. 2001 Dec;82(Pt 12):3011-9. http://www.ncbi.nlm.nih.gov/pubmed/11714978

 

Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case history and review

Abstract:

The spectrum of disease caused by parvovirus B19 has been expanding in recent years because of improved and more sensitive methods of detection. There is evidence to suggest that chronic infection occurs in patients who are not detectably immunosuppressed.

We report the case of a young woman with recurrent fever and a syndrome indistinguishable from chronic fatigue syndrome. After extensive investigation, we found persistent parvovirus B19 viremia, which was detectable by polymerase chain reaction (PCR) despite the presence of IgM and IgG antibodies to parvovirus B19.

Testing of samples from this patient suggested that in some low viremic states parvovirus B19 DNA is detectable by nested PCR in plasma but not in serum. The patient’s fever resolved with the administration of intravenous immunoglobulin.

 

Source: Jacobson SK, Daly JS, Thorne GM, McIntosh K. Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case history and review. Clin Infect Dis. 1997 Jun;24(6):1048-51. http://cid.oxfordjournals.org/content/24/6/1048.long (Full article)

 

New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6

Abstract:

The paper describes events that in the last fifteen years, have led to the identification of the aetiological agents of three widely known diseases: cat scratch disease, erythema infectiosum and exanthem subitum. The particular features of Afipia felis and Rochalimaea, Parvovirus B 19 and Herpesvirus 6 are presented.

The paternity of new diseases (i.e. bacillary angiomatosis, bacillary peliosis hepatitis, LES-like syndrome, chronic fatigue syndrome, petechial glove and sock syndrome, etc.) has also been attributed to some of these pathogens as has the paternity of some older ones (i.e. aplastic crisis, erythroblastosis fetalis, trench fever, hepatitis, opportunistic infection, etc.).

It has been argued that the same pathogen can cause different diseases depending on the immunogenic state of the subject. To date, persisting difficulties in isolating the pathogen or differentiating between latent or active infection, still in some cases raises doubts concerning the attribution of the disease to a specific agent.

New immunological or molecular techniques, allowing the direct detection of in vivo replication, are still needed in order to establish a sure connection between some of these agents and some of these diseases. Progress here will both give more accurate data about the epidemiology of some diseases and allow us to apply more appropriate treatment and prevention techniques.

 

Source: Zannolli R, Morgese G. New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6. Panminerva Med. 1995 Dec;37(4):238-47. http://www.ncbi.nlm.nih.gov/pubmed/8710408

 

Absence of parvovirus B19 infection in chronic fatigue syndrome

Abstract:

OBJECTIVE: To evaluate the presence of infection with parvovirus B19 in patients with chronic fatigue syndrome (CFS) who also had rheumatologic symptoms and mild hematologic abnormalities.

METHODS: Seven patients meeting the Centers for Disease Control and Prevention working case definition for CFS who also had mild leukopenia, thrombocytopenia, or anemia were studied. Bone marrow was aspirated from each patient, and examined for morphologic abnormalities, including features seen in marrow infections with parvovirus B19, as well as for parvoviral DNA, using polymerase chain reaction (PCR) amplification. Serum obtained at the time of marrow aspiration was also evaluated for parvoviral DNA, using the PCR method, and was examined for the presence of IgM and IgG antibodies to the virus.

RESULTS: No evidence of marrow involvement with parvovirus B19 was found in any patient. One patient had antibody evidence of a transient parvoviral infection, during which time an underlying thrombocytopenia worsened.

CONCLUSION: Despite examining a selected group of patients thought most likely to have parvoviral infection, based on clinical and hematologic measures, no evidence of clinically important parvoviral infection was noted. Thus, it seems unlikely that parvovirus B19 plays a role in CFS, even though it has been associated with fibromyalgia, a clinically similar syndrome.

 

Source: Ilaria RL Jr, Komaroff AL, Fagioli LR, Moloney WC, True CA, Naides SJ. Absence of parvovirus B19 infection in chronic fatigue syndrome. Arthritis Rheum. 1995 May;38(5):638-41. http://www.ncbi.nlm.nih.gov/pubmed/7748220

 

Parvovirus B19 infection–persistence and genetic variation

Abstract:

53 patients with acute B19 infection were studied; symptoms at acute infection were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine fetal death (n = 1). These patients were followed for 26-85 months (mean 57 months) and re-assessed for persistent symptoms, anti-B19 antibodies, and B19 DNA. At follow-up, 7 individuals were positive for serum B19 DNA, compared with none of the controls (2-tailed p value = 0.016). All 7 of those persistently infected were women, 3 of whom had symptoms; 1 had a chronic haemolytic anaemia (initial presentation was aplastic crisis); 1 had persistent arthralgia in both knees (initial presentation was bilateral knee arthralgia); and 1 had arthralgia in one knee and chronic fatigue syndrome (initial presentation was bilateral arthralgia in knees and shoulders). For the 7 persistently infected patients, serum from the time of diagnosis of acute B19 infection was available for 4, all of which contained B19 DNA. With single-stranded conformational polymorphism (SSCP) assay of these 11 PCR products, identical SSCP types were demonstrated in 5 of 7 follow-up isolates. In 2 of the 4 cases for which both acute and follow-up PCR product was available, the SSCP type of the follow-up product was different from that of the acute product. Two B19 virus types were demonstrated in one patient (with persistent arthralgia and chronic fatigue syndrome) at follow-up assessment.

 

Source: Kerr JR, Curran MD, Moore JE, Murphy PG. Parvovirus B19 infection–persistence and genetic variation. Scand J Infect Dis. 1995;27(6):551-7. http://www.ncbi.nlm.nih.gov/pubmed/8685632

 

Fibromyalgia and parvovirus infection

Abstract:

An infectious cause of fibromyalgia (FM) has been hypothesized based upon the observed similarity of this entity and chronic fatigue syndrome. Three patients developed symptoms of FM after documented episodes of acute parvovirus B19 infections. B19 antibody determinations were obtained approximately 1 month after the symptoms began; both IgM and IgG titers were positive at that time. All 3 patients met criteria for FM. Polysomnography performed on 2 of the patients revealed profound alpha-wave intrusion throughout nonrapid eye movement sleep. A more careful search for viral infections in FM patients whose symptoms appear following a “flu-like” illness appears warranted.

 

Source: Leventhal LJ, Naides SJ, Freundlich B. Fibromyalgia and parvovirus infection. Arthritis Rheum. 1991 Oct;34(10):1319-24. http://www.ncbi.nlm.nih.gov/pubmed/1657005